| First Author | Wei W | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 23 | Pages | 4692-705 |
| PubMed ID | 21947280 | Mgi Jnum | J:178880 |
| Mgi Id | MGI:5300446 | Doi | 10.1128/MCB.05979-11 |
| Citation | Wei W, et al. (2011) Osteoclast progenitors reside in the peroxisome proliferator-activated receptor gamma-expressing bone marrow cell population. Mol Cell Biol 31(23):4692-705 |
| abstractText | Osteoclasts are bone-resorbing cells essential for skeletal development, homeostasis, and regeneration. They derive from hematopoietic progenitors in the monocyte/macrophage lineage and differentiate in response to RANKL. However, the precise nature of osteoclast progenitors is a longstanding and important question. Using inducible peroxisome proliferator-activated receptor gamma (PPARgamma)-tTA TRE-GFP (green fluorescent protein) reporter mice, we show that osteoclast progenitors reside specifically in the PPARgamma-expressing hematopoietic bone marrow population and identify the quiescent PPARgamma(+) cells as osteoclast progenitors. Importantly, two PPARgamma-tTA TRE-Cre-controlled genetic models provide compelling functional evidence. First, Notch activation in PPARgamma(+) cells causes high bone mass due to impaired osteoclast precursor proliferation. Second, selective ablation of PPARgamma(+) cells by diphtheria toxin also causes high bone mass due to decreased osteoclast numbers. Furthermore, PPARgamma(+) cells respond to both pathological and pharmacological resorption-enhancing stimuli. Mechanistically, PPARgamma promotes osteoclast progenitors by activating GATA2 transcription. These findings not only identify the long-sought-after osteoclast progenitors but also establish unprecedented tools for their visualization, isolation, characterization, and genetic manipulation. |
